In the present project we will attempt to identify the parameters of intermediary metabolism that may be of importance for cellular radiation sensitivity, and utilize the knowledge gained to devise improved schemes for enhancement of radiation response. Initially, we will attempt to poise cells in vitro at high and low levels of the potential intracellular radical scavengers, reduced pyridine nucleotides and non-protein sulfhydryl compounds, independent of the oxygen tension, and determine the radiation senstivity of the system in terms of cell survival. Agents that will be used include normal metabolites (such as glucose, pyruvate, phosphate), substrate analogs, specific inhibitors, and insulin. The cells will be tested under both anoxic and hypoxic (0- 10mm O2) conditions, as well as in the presence of air. The biochemistry of the hypoxic cell will be studied in greater detail; of special interest is the relationship between glycolysis and respiration at low oxygen tension. Also, the effect on cell survival and on pot- irradiation repair of altered metabolism as well as of the agents and substrates used, will be determined. Eventually, we plan to test our results with radiation on animal tumors in vivo.